HA14-1, a small molecule inhibitor of Bcl-2, bypasses chemoresistance in leukaemia cells

We analyzed the biological activity of HA14-1, a small organic compound inhibitor of Bcl-2, against established leukaemia cell lilies and blasts from acute myeloid leukaemia (AML) patients. HA14-1 had a potent killing activity against the leukaemia cell line that expressed endogenous or ectopic Bcl-2. This activity was mostly caspase-independent and was not altered by the expression of a multidrug-resistant phenotype. Moreover. HA14-1 efficiently induced cell death in a broad spectrum of AML blasts but not in normal peripheral blood lymphocytes. Thus, sin-le-agent regimens using Bcl-2 inhibitors such as HA14-1 may be advantageous in overcoming some forms of chemoresistance in AML. (c) 2006 Elsevier Ltd. All rights reserved.